Y-box binding protein-1 promotes castration-resistant prostate cancer growth via androgen receptor expression
Y-box binding protein-1 promotes castration-resistant prostate cancer growth via androgen receptor expression
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DOI：
10.1530/erc-11-0017
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发表时间：
2011-08-01
影响因子：
3.9
通讯作者：
Naito, Seiji
中科院分区：
文献类型：
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作者：
Shiota, Masaki;Takeuchi, Ario;Naito, Seiji
雄激素受体（AR）在前列腺癌（PCa）的发病机制中起重要作用。在几项研究中，AR在去势抵抗性PCa（CRPC）中过表达。然而，CRPC中AR过表达的机制尚未完全阐明。Y盒结合蛋白-1（YB-1）是一种在CPRC中上调的多效性转录因子。我们的目的是阐明YB-1在前列腺癌去势抵抗中的作用，并确定以YB-1为靶点的治疗潜力。免疫组化结果显示，前列腺癌组织中YB-1的表达与Gleason评分和AR表达显著相关。在PCa细胞中，YB-1在转录水平上调节AR的表达。此外，CRPC细胞中YB-1表达和核定位上调。AR以及YB-1的过表达在LNCaP和22 Rv 1细胞中赋予去势抵抗性生长。相反，敲低YB-1导致细胞生长抑制和诱导凋亡，这比敲低LNCaP细胞中的AR更有效。在其他类型的PCa细胞（例如CRPC细胞）中，敲除YB-1会导致细胞生长显着减少。总之，这些发现表明YB-1通过AR表达诱导雄激素依赖性PCa细胞的去势抵抗。因此，YB-1可能是PCa以及CRPC的有希望的治疗靶点。内分泌相关癌症（2011）18 505-517
The androgen receptor (AR) is well known to play a central role in the pathogenesis of prostate cancer (PCa). In several studies, AR was overexpressed in castration-resistant PCa (CRPC). However, the mechanism of AR overexpression in CRPC is not fully elucidated. Y-box binding protein-1 (YB-1) is a pleiotropic transcription factor that is upregulated in CPRC. We aimed to elucidate the role of YB-1 in castration resistance of PCa and identify therapeutic potential of targeting YB-1. Using immunohistochemistry, we found that nuclear YB-1 expression significantly correlated with the Gleason score and AR expression in PCa tissues. In PCa cells, YB-1 regulated AR expression at the transcriptional level. Furthermore, YB-1 expression and nuclear localization were upregulated in CRPC cells. Overexpression of AR, as well as YB-1, conferred castration-resistant growth in LNCaP and 22Rv1 cells. Conversely, knocking down YB-1 resulted in suppressed cell growth and induced apoptosis, which was more efficient than knocking down AR in LNCaP cells. In other types of PCa cells, such as CRPC cells, knocking down YB-1 resulted in a significant reduction of cell growth. In conclusion, these findings suggested that YB-1 induces castration resistance in androgen-dependent PCa cells via AR expression. Thus, YB-1 may be a promising therapeutic target for PCa, as well as CRPC. Endocrine-Related Cancer (2011) 18 505-517